Linear oligopeptide formation from alanine-diketopiperazine in acidic aqueous solutions using interfacial nano-pulsed discharge plasma†

Abstract

Traditionally, synthesis of peptides using solid- or liquid-phase methods requires organic solvents, which goes against the fundamentals of green chemistry. In our previous study, we successfully demonstrated a green synthesis process involving alanine oligopeptides from alanine–diketopiperazine (alanine–DKP) using pulsed discharge plasma. By optimizing the conditions for oligopeptide synthesis, we improved the green synthesis of alanine oligopeptides by performing plasma irradiation in an acidic aqueous solution. The yield of alanyl–alanyl–alanine from alanine–DKP is approximately 30% within 3–20 min. The addition of alanylalanine enhances the formation of higher oligopeptides. Furthermore, LC-MS analysis shows trace amounts of glycine–DKP, glycine oligopeptides, glutamic acid, pyruvic acid, and pyroglutamic acid, which implies the reaction mechanism for the spontaneous elongation of higher oligopeptides from alanine–DKP through the ring opening of alanine–DKP and the radical formation of amino acids. Thus, the formation of DKP is advantageous for the formation of oligopeptides and does not inhibit oligopeptide elongation. This study provides useful insights into the chemical evolution of oligopeptides and the development of environmentally friendly oligopeptide formation processes.